Evaluation of the prognostic value of TGF-β superfamily type I receptor and TGF-β type II receptor expression in nasopharyngeal carcinoma using high-throughput tissue microarrays
Evaluation of the prognostic value of TGF-β superfamily type I receptor and TGF-β type II receptor expression in nasopharyngeal carcinoma using high-throughput tissue microarrays
复制标题
DOI：
10.1007/s10735-012-9392-4
复制
发表时间：
2012-06-01
影响因子：
3.2
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Zhang, Wenling;Zeng, Zhaoyang;Li, Guiyuan
基因表达谱分析显示，TGF-β超家族I型受体（又称活化素受体样激酶1，ALK 1）和TGF-β R2（TGF-β II型受体）在鼻咽癌中表达下调（P < 0.05）。然而，目前还没有关于ALK 1和TGF β R2与NPC进展或患者结局相关性的大样本临床研究报道。本研究旨在评估ALK 1和TGF β R2表达与NPC进展的可能相关性及其在NPC结局中的潜在预后预测能力。采用qRT-PCR和组织芯片（TMA）检测742例鼻咽癌组织中ALK 1和TGF β R2的mRNA和蛋白水平。癌组织中ALK 1和TGF β R2的mRNA和蛋白水平均显著低于癌旁组织（P < 0.05）。鼻咽癌中EB病毒小RNA（EBER-1）杂交信号与ALK 1和TGF β R2蛋白表达显著相关（P分别为0.000和0.003）。Logistic回归分析显示，ALK 1和TGF β R2的异常表达是鼻咽癌发生的独立因素（P值分别为0.000和0.000）。生存分析显示ALK 1（无病生存期（DFS）：P = 0.002，总生存期（OS）：P = 0.007）和TGF β R2（DFS：P = 0.072，OS：P = 0.045）可预测鼻咽癌患者的预后。多因素分析显示ALK 1和TGF β R2阳性表达是DFS和OS的独立危险因素（DFS：P分别为0.001和0.420; OS：P分别为0.018和0.047）。这些结果表明，ALK 1和TGF β R2可能是有用的预后生物标志物在NPC。
Gene expression profiling had revealed that TGF-beta superfamily type I receptor (also known as activin receptor-like kinase-1, ALK1) and TGF beta R2 (TGF-beta type II receptor) were down-regulated in nasopharyngeal carcinoma (NPC) (P < 0.05, respectively). However, no study with significantly large clinical samples to address the relevance of ALK1 and TGF beta R2 in NPC progression or in patient outcomes has been reported. This study aims to assess the possible correlations of ALK1 and TGF beta R2 expression with NPC progression and their potential prognostic predictive ability in NPC outcomes. ALK1 and TGF beta R2 mRNA and protein levels were detected by qRT-PCR and NPC tissue microarray (TMA), which included 742 tissue cores. Both mRNA and protein levels of ALK1 and TGF beta R2 were significantly lower in the cancer tissues compared with the non-cancerous tissues (P < 0.05). Epstein-Barr virus small RNA (EBER-1) hybridization signals in NPC showed significant associations with ALK1 and TGF beta R2 proteins (P = 0.000 and 0.003, respectively). In the final logistic regression analysis model, the abnormal expression of ALK1 and TGF beta R2 were found to be independent contributors to nasopharyngeal carcinogenesis (P = 0.000 and 0.000, respectively). A survival analysis revealed that ALK1 (Disease Free Survival (DFS): P = 0.002, Overall Survival (OS): P = 0.007) and TGF beta R2 (DFS: P = 0.072, OS: P = 0.045) could predict the prognosis of NPC patients. The positive expression of ALK1 and TGF beta R2 were independent risk factors for DFS and OS in multivariate analyses (DFS: P = 0.001 and 0.420, respectively; OS: P = 0.018 and 0.047, respectively). These results suggest that ALK1 and TGF beta R2 may be useful prognostic biomarkers in NPC.